The present invention relates to processes for the preparation of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof, and (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof. These compounds are known to be useful for treating e.g., depression, anxiety disorders, eating disorders and urinary incontinence (see U.S. Pat. Nos. 6,372,919, 6,569,887 and 6,716, 868).
The general processes disclosed in the art for the preparation of racemic, (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane and (−)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane result in relatively low and inconsistent yields of the desired product (see e.g., U.S. Pat. Nos. 4,118,417, 4,131,611, 4,196,120, 4,231,935, 4,435,419, 6,372,919, 6,569,887, 6,716, 868: Sorbera, et al., Drugs Future 2005, 30, 7; and Epstein, et al., J. Med. Chem., 1981, 24, 481). Some of such processes rely on the use of expensive reagents. In contrast to the previously known processes, the present invention provides effective methodology for the preparation of (+) or (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in relatively high yield and enantiomeric purity. It will be appreciated that (+) and (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane are useful therapeutic agents. As such, there is a need for the development of processes for the preparation of (+) and (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane which are readily amenable to scale-up, use cost-effective and readily available reagents, and which are therefore capable of practical application to large scale manufacture. Accordingly, the subject invention provides a process for the preparation of (+) and (−)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane via a very simple, short and highly efficient synthesis.